This year, we have continued our physiological studies in neurological and psychiatric patients and healthy individuals in collaboration with the Laboratory of Clinical Science, NIMH. We have investigated the changes in cortical excitability that take place in the motor cortex when individuals learn a motor sequence and have found that patients with obsessive compulsive disorder (OCD) do not show the normal increase in excitability, perhaps because this mechanism is already facilitated. In this area, we have also published data showing that the degree of intracortical inhibition is correlated with personality variables related to anxiety and negative emotion, which may account for our earlier findings on this measure in OCD. In another effort, we have found effects excitatory of estrogen on the motor cortex in healthy women and evidence that the inhibitory effect of pregesterone metabolites that we described previously may be altered in women with premenstrual syndrome. Priming stimulation has been shown repeatedly to increase the ability of 1 Hz stimulation to produce long-term depression in hippocampal synapses. Since 1 Hz repetitive transcranial magnetic stimulation (TMS) produces robust depression of the excitability in the motor cortex, we started a study in healthy individuals to look at the effect of 6 Hz priming stimulation on this effect. Preliminary data suggest that motor cortex depression from 1 Hz stimulation is longer-lasting when preceded 6 Hz priming. If borne out in more subjects, priming stimulation may make TMS treatments more effective in disorders such as epilepsy.